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Lapatinib Study for Children and Adults With Neurofibromatosis Type 2 (NF2) and NF2-Related Tumors

Primary Purpose

Neurofibromatosis 2, Vestibular Schwannoma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Lapatinib

About this trial

This is an interventional treatment trial for Neurofibromatosis 2 focused on measuring NF-2, NF-2 related tumors, Schwannoma, Acoustic, Bilateral, schwannomas, Neurilemmoma of other cranial and peripheral nerves, NF2 related benign intracranial tumors including, NF2 related meningiomas, NF2 related ependymomas, NF2 related spinal neurofibromas, NF2 related gliomas

Eligibility Criteria

4 Years - 80 Years (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Patients must be at least 4 years of age.
Patients must meet diagnostic criteria for NF2 and at least one volumetrically measured NF2-related brain or spinal tumor with radiographic evidence of progression over the past 12 months, designated as the primary target OR volumetrically measurable VS with ipsilateral progressive hearing loss over the past 12 months, designated as the primary target tumor.
Significant hearing loss criteria for enrollment.
Karnofsky (PS) OR Lansky 50-100% (>16 years of age)
Absolute neutrophil count ≥ 1,000/mm3 g/dL
Hemoglobin ≥ 8 g/dL
Creatinine ≤ 1.5 times upper limit of normal (ULN) OR corrected glomerular filtration rate ≥ 70 ml/min
Bilirubin ≤ 1.5 times ULN
ALT ≤ 2.5 times ULN
Fully recovered from acute toxic effects of any prior chemotherapy, biological modifiers or radiotherapy.
Steroids are allowed for progressive symptoms but patient must be on a stable dose for at least 1 week prior to study entry.
Any neurologic deficits must be stable for ≥ 1 week.
Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Women of childbearing potential must have a negative pregnancy test. The anti-proliferative activity of this experimental drug may be harmful to the developing fetus.
Normal cardiac left ventricular ejection fraction (LVEF) by transthoracic echocardiogram.
Able to provide written informed consent (or consent by parent/legal guardian for minors)

Exclusion Criteria:

Patients with serious concurrent infection or medical illness.
Neurological deficits that are rapidly progressing.
Patients who are pregnant or breast-feeding.
Anti-tumor therapy within 4 weeks prior to enrollment.
Radiation therapy within 2 months prior to enrollment.
Prior therapy with agents targeting EGFR or ErbB2.
Any surgery within 4 weeks prior to enrollment.
Significant gastrointestinal disorder(s)
Known cardiac disease
Patients with a concurrent or prior malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin. Patients who have been free of disease (any prior malignancy) for more than five years are eligible for this study.
Patients cannot have received cytochrome P450-inducing anticonvulsants (EIADs; e.g., phenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine) or similar agents (e.g., rifampin) or P450-inhibiting agents (Ketoconazole, Itraconazole, Clarithromycin, Atazanavir, Indinavir, Nefazodone, Nelfinavir, Ritonavir, Saquinavir, Telithromycin, Voriconazole)

Sites / Locations

New York University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lapatinib

Arm Description

Lapatinib PO dosed according to age: Children/adolescents (less than 18 years of age): 1,800 mg/m2/day PO divided into twice daily doses, to a maximum of 750 mg PO twice daily Adults (18 years of age or older): 1,500 mg PO once daily Lapatinib is available in 250 mg tablets only. For pediatric dosing, the total daily dose will be rounded up or down to the nearest 250 mg increment.

Outcomes

Primary Outcome Measures

Estimated Volumetric Progression Free Survival at 12 Months

Measurements were taken every three months, up to one year. Estimated volumetric progression free survival (PFS) was measured from date of enrollment to date of volumetric progression. PFS was analyzed using the Kaplan-Meier method in terms of overall PFS (volumetric or hearing progression), volumetric progression, and hearing progression. Point estimates for PFS with 95% confidence intervals (CIs) were calculated from Kaplan-Meier curves.

Secondary Outcome Measures

Estimated Volumetric Progression Free Survival for Hearing at 12 Months

Measurements were taken every three months, up to one year. Estimated volumetric progression free survival (PFS) was measured from date of enrollment to date of hearing progression. PFS was analyzed using the Kaplan-Meier method in terms of overall PFS (volumetric or hearing progression), volumetric progression, and hearing progression. Point estimates for PFS with 95% confidence intervals (CIs) were calculated from Kaplan-Meier curves.

Participants Experiencing Grades 1 or 2 Toxicities (CTCAE)

Toxicity was assessed throughout the study, up to one year.

Participants Experiencing Grade 3 Toxicities (CTCAE)

Toxicity was assessed throughout the study, up to one year.

Full Information

NCT ID

NCT00973739

First Posted

September 3, 2009

Last Updated

February 19, 2016

Sponsor

NYU Langone Health

Collaborators

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT00973739

Brief Title

Lapatinib Study for Children and Adults With Neurofibromatosis Type 2 (NF2) and NF2-Related Tumors

Official Title

Phase II Study of Lapatinib in Children and Adults With Neurofibromatosis Type 2(NF2) and NF2-related Tumors

Study Type

Interventional

2. Study Status

Record Verification Date

February 2016

Overall Recruitment Status

Completed

Study Start Date

September 2009 (undefined)

Primary Completion Date

October 2012 (Actual)

Study Completion Date

November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

NYU Langone Health

Collaborators

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to determine if Lapatinib has any effect on tumors found in patients with Neurofibromatosis Type 2 (NF2). NF2 is a condition that mainly affects the skin and nervous system. It causes non-cancerous tumors (which are known as neuromas) to grow on the nerves around a person's body. Some signs of NF2 include a gradual loss of hearing and tumors growing on the skin, the brain and the spinal cord which can lead to complications. Lapatinib is an oral drug that is approved by Food and Drug Administration (FDA) for other types of tumors, it is not approved by the FDA for treatment of NF2 related tumors. The investigators know a lot about how well it is tolerated, but the investigators do not know if it is effective in treating your condition, therefore it is considered to be an investigational medication. This study will test whether Lapatinib may shrink tumors commonly found in patients with NF2 or stop them from growing. This will help us to decide if Lapatinib should be used to treat NF2 patients in future. Lapatinib is a drug that has been used for over 10 years to treat various forms of cancer. It has not been studied for the treatment of tumors in NF2 patients.

Detailed Description

In this trial, we propose to assess the objective response rates to Lapatinib in patients with NF2-related tumors. Lapatinib is a commercially available inhibitor of ErbB2 and EGF. Data suggests that abnormal signaling via EGFR and ErbB2 is a major contributor to tumor growth and progression in both sporadic and NF2-related VS and that inhibition of this signaling pathway can result in decreased tumor growth. Demonstrating that Lapatinib produces an objective response to reduce tumor volume or stabilize disease will provide additional treatment options for NF patients with multiple tumor growth. For patients with VS we expect to see ≥ 10 dB improvement in PTA and/or improvement in SDS, compared to the audiogram at initiation of treatment. Currently there are no available treatment options for NF2 patients with multiple tumors. Depending on tumor cell type, lapatinib has cytostatic or cytotoxic antitumor effects, and in a recent study assessing the biological effects of Lapatinib on the associated molecular pathways and tumor growth in patients with solid tumors, a correlation was seen between tumor response and pre-treatment levels of (phosphor)-ErbB2 and (phosphor)-ERK1/2.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neurofibromatosis 2, Vestibular Schwannoma

Keywords

NF-2, NF-2 related tumors, Schwannoma, Acoustic, Bilateral, schwannomas, Neurilemmoma of other cranial and peripheral nerves, NF2 related benign intracranial tumors including, NF2 related meningiomas, NF2 related ependymomas, NF2 related spinal neurofibromas, NF2 related gliomas

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lapatinib

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Lapatinib

Other Intervention Name(s)

Tykerb

Intervention Description

Lapatinib is dosed according to age. Lapatinib is available in 250 mg tablets only. For pediatric dosing, the total daily dose will be rounded up or down to the nearest 250 mg increment. Children/adolescents (<18 years of age): 1,800 mg/m2/day PO divided into twice daily doses, to a maximum of 750 mg PO (3 tablets twice daily) Adults (>=18 years of age): 1,500 mg PO (6 tablets once daily) Duration: Up to 12 months, depending on treatment response.

Primary Outcome Measure Information:

Title

Estimated Volumetric Progression Free Survival at 12 Months

Description

Time Frame

Every three months for one year

Secondary Outcome Measure Information:

Title

Estimated Volumetric Progression Free Survival for Hearing at 12 Months

Description

Time Frame

Every three months for one year

Title

Participants Experiencing Grades 1 or 2 Toxicities (CTCAE)

Description

Toxicity was assessed throughout the study, up to one year.

Time Frame

Baseline through one year

Title

Participants Experiencing Grade 3 Toxicities (CTCAE)

Description

Toxicity was assessed throughout the study, up to one year.

Time Frame

Baseline through one year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

4 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must be at least 4 years of age. Patients must meet diagnostic criteria for NF2 and at least one volumetrically measured NF2-related brain or spinal tumor with radiographic evidence of progression over the past 12 months, designated as the primary target OR volumetrically measurable VS with ipsilateral progressive hearing loss over the past 12 months, designated as the primary target tumor. Significant hearing loss criteria for enrollment. Karnofsky (PS) OR Lansky 50-100% (>16 years of age) Absolute neutrophil count ≥ 1,000/mm3 g/dL Hemoglobin ≥ 8 g/dL Creatinine ≤ 1.5 times upper limit of normal (ULN) OR corrected glomerular filtration rate ≥ 70 ml/min Bilirubin ≤ 1.5 times ULN ALT ≤ 2.5 times ULN Fully recovered from acute toxic effects of any prior chemotherapy, biological modifiers or radiotherapy. Steroids are allowed for progressive symptoms but patient must be on a stable dose for at least 1 week prior to study entry. Any neurologic deficits must be stable for ≥ 1 week. Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Women of childbearing potential must have a negative pregnancy test. The anti-proliferative activity of this experimental drug may be harmful to the developing fetus. Normal cardiac left ventricular ejection fraction (LVEF) by transthoracic echocardiogram. Able to provide written informed consent (or consent by parent/legal guardian for minors) Exclusion Criteria: Patients with serious concurrent infection or medical illness. Neurological deficits that are rapidly progressing. Patients who are pregnant or breast-feeding. Anti-tumor therapy within 4 weeks prior to enrollment. Radiation therapy within 2 months prior to enrollment. Prior therapy with agents targeting EGFR or ErbB2. Any surgery within 4 weeks prior to enrollment. Significant gastrointestinal disorder(s) Known cardiac disease Patients with a concurrent or prior malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin. Patients who have been free of disease (any prior malignancy) for more than five years are eligible for this study. Patients cannot have received cytochrome P450-inducing anticonvulsants (EIADs; e.g., phenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine) or similar agents (e.g., rifampin) or P450-inhibiting agents (Ketoconazole, Itraconazole, Clarithromycin, Atazanavir, Indinavir, Nefazodone, Nelfinavir, Ritonavir, Saquinavir, Telithromycin, Voriconazole)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Matthias A Karajannis, MD, MS

Organizational Affiliation

NYU School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

New York University School of Medicine

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

12. IPD Sharing Statement

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Lapatinib Study for Children and Adults With Neurofibromatosis Type 2 (NF2) and NF2-Related Tumors

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